1. Field of the Invention
The present invention relates to a method of creating biological and biosynthetic material suitable for implantation to replace or augment damaged, diseased or absent tissues, structures or organs, of particular but by no means exclusive application in the treatment of autogenic, allogenic or xenogenic material of mammalian origin, to maintain a microarchitectural organization and inhibit in vivo calcification, tissue ingrowth and transmural angiogenesis. In one embodiment, as may be determined by the end use, transplanted living cells can be attached and retained under in vivo conditions.
2. Description of Related Art
Tissue stabilization and fixation using, for example, glutaraldehyde to impart strength, neutralize antigenic sites and sterilize biosynthetic and biological tissue for human implantation has been described previously. U.S. Pat. Nos. 4,319,363, 4,466,139 and 4,681,588 (Ketharanathan) disclose the processing of biosynthetic and biological material at a constant concentration of glutaraldehyde and at a constant pH in a static fluid environment in order to impart strength and durability, neutralize antigenic sites and sterilize the material. U.S. Pat. No. 3,966,401 (Hancock and Fogarty) describes a method of pressurizing tissues, such as those of a heart valve, with a tanning fluid such as glutaraldehyde, to within the physiological range, and releasing the pressure such that natural tissue retains flexibility. On the other hand U.S. Pat. No. 4,798,611 (Freeman) discloses a method of sterilizing, imparting compliance and reducing antigenecity by gamma radiating xenog nic material at a 1 vel of 2 to 8 megarads following treatment with a cross linking agent, for example, glutaraldehyde.
In vivo calcification has been reported in implanted glutaraldehyde treated biological tissue prostheses, particularly heart valve prostheses. In vivo micro-calcification was demonstrated in the wall of the material of U.S. Pat. No. 4,466,139 when used as a vascular conduit in dogs, though the calcification did not cause the material to fail. Storage in 50% alcohol prior to implantation reduced but did not eliminate the degree of calcification. A number of methods have been instituted in an effort to reduce or eliminate calcification. U.S. Pat. No. 4,648,881 (Carpentier et al.) describes a method of inhibiting calcification in biological tissue by the use of phosphate deficient solution, and U.S. Pat. No. 5,931,969 (Carpentier et al.) discloses treating at least partially fixed tissue in a heated treatment solution and inducing tissue/solution movement for between 15 and 60 days. In U.S. Pat. No. 5,843,181 (Jaffe and Hancock) a method is disclosed whereby biological tissue is made substantially acellular by exposure to at least one buffered solution with a pH in the range of 5 to 8 prior to fixation. U.S. Pat. No. 5,746,775 (Levy and Hirsch) discloses the inhibiting of in vivo calcification by subjecting tissue to an aqueous solution of 60 to 80% lower aliphatic alcohol containing an anti-calcification agent for at least 20 minutes following glutaraldehyde pre-treatment.
Various methods of pre-treatment of substrates with extracellular matrix proteins to emulate a protein surface, in an effort to promote growth, attachment and retention of living transplanted cells onto the surface of synthetic materials, have been documented. For example, coating polyester graft material with human plasma and fibrin gel for the attachment of endothelial cells on synthetic vascular graft surfaces to provide at least 50% confluence is disclosed in U.S. Pat. No. 4,820,626 (Williams and Jarrell). U.S. Pat. No. 5,632,778 (Goldstein) describes a method of killing native cello in interstitial collagen, removing potentially immunogenically active soluble molecules and subsequently treating the acellular tissue with extracellular substances and transplanting allogenic or autologous cells prior to implantation of the graft material.
Considerable attention has been paid to the appropriate pore size of synthetic materials for implantation in order to promote healing or biolisation via tissue ingrowth and more recently for transmural angiogenisis to promote endothelialisation. An unwanted aspect is the uncontrolled nature of tissue ingrowth particularly in vascular conduits of 6 mm internal diameter and less which causes lumenal narrowing, thrombosis and occlusion with subsequent graft failure.